Human immune response to HIV-1 Nef. II. Induction of HIV-1/HIV-2 Nef cross-reactive cytotoxic T lymphocytes in peripheral blood lymphocytes of non-infected healthy individuals

Abstract

HIV-specific CD8+ cytotoxic T lymphocytes (CTL) are thought to have a beneficial role in HIV infection. In a previous report we have shown that HIV-1 Nef-specific CTL can be readily induced in peripheral blood lymphocytes of seronegative healthy young adults by in vitro stimulation with autologous Epstein-Barr virus-transformed B lymphoblastoid cell lines transfected with the HIV-1 nef gene. Here we demonstrate that these Nef-specific CTL can efficiently lyse HIV-infected primary CD4+ T lymphocytes. CTL of the blood donor tested were Nef-specific and restricted by the autologous MHC class I molecules HLA-A2 and HLA-B7. They recognized HIV-1 Nef in association with both restriction elements but HIV-2 Nef only in association with HLA-B7. The cross-reactivity of the induced effector cells together with the potent immunogenicity of Nef in healthy seronegatives further support the inclusion of Nef as a constituent of HIV vaccines.